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<p>Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged ≤70 years 1:1 to isatuximab–carfilzomib–lenalidomide–dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10<sup>−5</sup> or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10<sup>−6</sup> or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10<sup>−5</sup> (77% versus 67%; odds ratio (OR) 1.67, <i>P</i> = 0.049) and 10<sup>−6</sup> (68% versus 48%; OR 2.36, <i>P</i> = 0.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10<sup>−5</sup> 46% versus 27%, OR 2.32, <i>P</i> = 0.0007; 10<sup>−6</sup> 28% versus 14%, OR 2.44, <i>P</i> = 0.0029) and durable (1-year sustained 10<sup>−6</sup> MRD negativity 52% versus 38%, OR 1.82, <i>P</i> = 0.012). At current follow-up, PFS data were immature. Grade 3–4 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration: <a href="https://clinicaltrials.gov/study/NCT04483739">NCT04483739</a>.</p>

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Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial

  • 期刊论文

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  • 发表日期：

    2026年4月6日

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  • Francesca Gay,
  • Wilfried Roeloffzen,
  • Meletios A. Dimopoulos,
  • Laura Rosiñol,
  • Marjolein van der Klift,
  • Roberto Mina,
  • Albert Oriol,
  • Eirini Katodritou,
  • Ka Lung Wu,
  • Paula Rodríguez Otero,
  • Roman Hájek,
  • Elisabetta Antonioli,
  • Mark van Duin,
  • Mattia D’Agostino,
  • Joaquín Martínez-López,
  • Elena M. van Leeuwen-Segarceanu,
  • Elena Zamagni,
  • Niels W. C. J. van de Donk,
  • Katja C. Weisel,
  • Luděk Pour,
  • Jakub Radocha,
  • Angelo Belotti,
  • Fredrik Schjesvold,
  • Joan Bladé,
  • Hermann Einsele,
  • Pieter Sonneveld,
  • Mario Boccadoro,
  • Annemiek Broijl

摘要

Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged ≤70 years 1:1 to isatuximab–carfilzomib–lenalidomide–dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10−5 or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10−6 or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10−5 (77% versus 67%; odds ratio (OR) 1.67, P = 0.049) and 10−6 (68% versus 48%; OR 2.36, P = 0.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10−5 46% versus 27%, OR 2.32, P = 0.0007; 10−6 28% versus 14%, OR 2.44, P = 0.0029) and durable (1-year sustained 10−6 MRD negativity 52% versus 38%, OR 1.82, P = 0.012). At current follow-up, PFS data were immature. Grade 3–4 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration: NCT04483739.